The fetus secretes insulin appropriately in response to a number of stimuli, particularly alteration of circulating glucose levels. Furthermore, we have recently demonstrated that in response to glucose, alanine or tolbutamide, the fetus secretes insulin in characteristic patterns, ones strikingly similar to those seen in the adult-onset diabetic in response to these same stimuli. A possible role for prostaglandins in inhibition of glucose-induced early phase insulin secretion has recently been demonstrated in the adult-onset diabetic. This role for prostaglandins has not yet been ascertained in the fetus. Effects of fetal insulin secretion are most evident in the infant of the diabetic mother. The macrosomia and increased adipose and glycogen stores seen in this condition strongly suggest an anabolic role for insulin in the channelling of fetal substrates for fuel or accretion purposes. A role for fetal glucagon secretion has yet to be delineated. Utilizing the chronically catheterized fetal lamb as our model, we wish to explore: a) the effects of prostaglandin inhibitors such as acetylsalicylic acid and indomethacin on glucose-induced insulin release in the fetus, thus further exploring the unusual similarity between lack of early phase insulin release in both the fetus and adult-onset diabetic; b) acute and chronic fetal glucagon infusions to test the hypothesis that circulating glucagon levels in the fetus are important in the regulation of umbilical glucose and alanine uptake; and c) the hypothesis that prolonged elevation of fetal glucose as seen in the fetus of the diabetic mother is the prime stimulant for the development of chronic fetal hyperinsulinism and subsequent macrosomia. Chronic fetal hyperglycemia may also be an inducer of early phase insulin secretion in utero, not normally seen in the fetal animal.